The field of microfluidics has a number of emerging applications in analytical chemistry and chemical processing. One task central to the operation of microfluidic devices is the ability to move small volumes of fluid through microchannels and to control fluid flow. Traditional approaches to microfluidic device fabrication employ microfabrication or micromachining of substrates to produce three-dimensional structures to channel fluid flow. However, fabrication of such structures as valves, mixers and even chambers becomes increasingly difficult as the scale of the device decreases.
In addition, fluid transport and handling at sub-millimeter scales is distinctly different from such transport at larger scales. The large surface forces, high shear and extensional rates (e.g., low Reynolds number and high Weissenberg number), arising between the fluid and the microfluidic channels can make approaches and structures useful at larger scales useless or even inoperable at microfluidic scales. For example, as the size of the fluid conduits decrease it becomes increasingly harder to pump fluid by pressure. Surface-tension-driven actuation is one approach for handling liquids on sub-millimeter and smaller scale, but control of surface wettability can be problematic at these scales.
In addition, with decreasing scale, pumps and valves with moving parts become less attractive from an economic perspective. To this extent, functionalization of surfaces with covalently bound molecules has been attempted. However, such approaches may simply shift the primary determinant of device cost from the micromachining step to the synthesis of the covalently bound molecules and their proper attachment to the surface.
Another area of application is in the field of point-of-care (POC) analyte sensors, e.g., blood electrolyte sensors. Traditionally, most hospital electrolyte tests are performed in large, multiple-analyte analyzers in a chemistry or medical laboratory. Vials of blood are drawn from the patient for sampling, and hours, and even days, may pass before the caregiver receives the results. Various technologies have been proposed to provide a POC analyte sensor, but ultimately, reliability of sensor data is important, if not critical, if decisions are to be made without the use of traditional laboratory tests.
For example, electrochemical sensors using ion-selective electrode technology have been tried as POC electrolyte sensors. One example of an ion-selective electrode POC sensor is the i-STAT system, available from the i-STAT Corporation. The i-STAT system utilizes a blood sample that is drawn from the patient and injected into a cartridge including micro-fabricated, ion-selective electrodes, a calibration fluid pouch, and plastic structures for directing fluid flow and storing waste. The fluid pouch, containing known concentrations of the analytes, is punctured at the onset of a test, and the calibration fluid passes over the sensors, allowing a one-point calibration. The fluid is then flushed into the waste container and the blood sample is drawn in for testing.
Interferants, especially in the measurement of analyte concentrations in biological samples, can render unreliable analyte concentration measurements. For example, many glucose meters intended for home use are susceptible to interference from redox active materials such as vitamin C. The list of potential interferants in analyte concentration measurements of biological samples is long, and includes ions, biochemicals, proteins, cells and cellular debris. Accordingly, the reliability of concentration measurements made using traditional microfluidic sensors can be in question. Moreover, traditional microfluidic sensors do not provide, and often cannot provide, an indication of whether their individual measurements are in error. As a result, physicians cannot necessarily rely solely on the measurement provided by a traditional microfluidic sensor; this is a serious drawback for use of microfluidic sensors as POC sensors as a replacement for more traditional laboratory analysis of, e.g., blood samples.
In addition, some microfluidic devices require electrical power for, e.g., fluid movement or other analytical functioning. Incorporating electrical power into a microfluidic device generally involves configuring the device to interface with a, typically large, base unit (see, e.g., WO 01/14064) or batteries. Not only do such devices often involve complex circuitry and are often expensive to produce, but they can also limit the ease of transport of the device, e.g., in POC applications.